2- ethyl propionate, from hydrolysis

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

Method Two, Albertson et al. (48, 49). Hydrolysis of ethyl o-acet-amido-a-carbethoxy-j8-(3-indole)-propionate or ethyl-o-carbethoigr-ae-benzamido-j8-(3-indolyl)-propionate essentially by the procedure of Snyder and Smith (74) to give 35% over-all yield of tryptophan based on indole. Smith and Sogn (732) prepared ethyl a-carbetiioi -S-indole-propionate from ethyl o-ketocyclopentanone carboxylate (A) but no tryptophan could be synthesized sinCe they were not able to brominate (A). Similarly, Elks et al. (245) were unable to brominate ethyl (2-carbethoxy-3-indolylmethyl) malonate in the o-position although Maurer and Moser (562) stated that they had synthesized tryptophan by this procedure. 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

The above directions are based upon the methods of Hoogewerff and Van Doip, as modified by Holm and by Hale and Honan. -Alanine has also been prepared by the action of h3q)obromite upon succinimide and hydrolysis of the resulting /3-ureidopropionic acid by the action of ammonia upon /3-iodo-propionic acid by the hydrolysis of methyl carbomethoxy-/8-aminopropionate, obtained by the action of sodiiun methoxide on succinbromimide by the reduction of 3-nitrosopropionic acid by heating ethyl acrylate with alcoholic ammonia from succinyl-glycine ester by the azide synthesis and by the action of liquid ammonia upon methyl acrylate. ... 

These compounds are prepared starting from chloroace-tic acid or its ethyl ester. For chains longer than acetic, cya-noethylation and hydrolysis of the nitrile obtained leads to the propionic chain, alkylation with ethyl 4-bromobutyrate and saponification leads to the butyric chain. The propane-sulfonic chains are particularly accessible by means of ring opening of propane-sultone. 

A membrane cell recycle reactor with continuous ethanol extraction by dibutyl phthalate increased the productivity fourfold with increased conversion of glucose from 45 to 91%.249 The ethanol was then removed from the dibutyl phthalate with water. It would be better to do this second step with a membrane. In another process, microencapsulated yeast converted glucose to ethanol, which was removed by an oleic acid phase containing a lipase that formed ethyl oleate.250 This could be used as biodiesel fuel. Continuous ultrafiltration has been used to separate the propionic acid produced from glycerol by a Propionibacterium.251 Whey proteins have been hydrolyzed enzymatically and continuously in an ultrafiltration reactor, with improved yields, productivity, and elimination of peptide coproducts.252 Continuous hydrolysis of a starch slurry has been carried out with a-amylase immobilized in a hollow fiber reactor.253 Oils have been hydrolyzed by a lipase immobilized on an aromatic polyamide ultrafiltration membrane with continuous separation of one product through the membrane to shift the equilibrium toward the desired products.254 Such a process could supplant the current energy-intensive industrial one that takes 3-24 h at 150-260X. Lipases have also been used to prepare esters. A lipase-surfactant complex in hexane was used to prepare a wax ester found in whale oil, by the esterification of 1 hexadecanol with palmitic acid in a membrane reactor.255 After 1 h, the yield was 96%. The current industrial process runs at 250°C for up to 20 h. 

The C-methyl derivatives (350) and (351) have been synthesized by hydrolysis and thiolysis of ethylidene bis(dibromoarsine) (349) (Equation (53)). The adamantane (350) was also synthesized simply by heating potassium arsenite with propionic acid in propionic anhydride <69ZAAC(370)3l>. The tetra-A-ethyl compound (352) was obtained from (349 Hal = Cl) by the same method as described for the synthesis of (348). 

Synthesis. DL-Tryptophan is synthesized in 70% over-all yield from crude indole by the method of Albertson and Tullar (50). Ethyl o-acetamido-a-cyano-/3-(3-indolyl)-propionate (A) is prepared in 98% yield from ethyl acetamidocyanoacetate , gramine (3-dimethylamino-methyl indole) , sodium, ethanol and ethyl iodide according to the procedure described by Albertson et al. (49). OL-Tryptophan is prepared by alkaline hydrolysis of (A). Other practicable syntheses of tryptophan which have been reported recently are outlined in the following equations. 

Sucrose was actylated at 0-1 preferentially by subtilisin-catatysed transesterification from the trifluoro- or trichloro- ethyl esters of acetic, propionic, octanoic, benzoic, and acrylic acid in DMF. Subsequent hydrolysis of the yoosidic bond with a-glucosidase gave D-fructose l-esters. ... 

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